The interaction of the T cell receptor (TCR) with its specific ligand, peptide-MHC, is only one component of the events required for the activation of antigen-specific T cells. The primary goals of our studies are to characterize cell surface antigens (co-receptors) and their soluble or cell associated ligands (counter-receptors) which play critical roles in cell-cell interaction and in the interaction of T cells with their environment. Our studies have focused in a number of distinct areas: 1) We have examined the accessory cell requirements for induction of CD40L expression on CD4+ T cells and demonstrated that expression of the B7 antigen was both necessary and sufficient for induction of the CD40L. To directly examine whether the B7/CD28 costimulatory pathway is the exclusive pathway for the induction of the CD40L, CD28 deficient mice were stimulated with anti-CD3 in vivo or in vitro. Induction of the CD40L was comparable on T cells from CD28 deficient mice and normal mice. These results demonstrate that costimulatory signals resulting from B7/CD28 interactions as well as a non-B7/CD28 pathway can result in effective induction of CD40L expression. 2) Integrins represent a candidate group of cell surface receptors that may control the homing and population of the thymus by T cell precursors and the subsequent migration of developing thymocytes through the thymic architecture. To further characterize the role of the integrins alpha4beta1 and alph5beta1 in thymocyte differentiation, we correlated the expression of these integrins with other markers of thymocyte differentiation. The earliest T cell precursors in the thymus selectively expressed both alpha4beta1 and alpha5beta1 at high levels and that these integrins may play a role in the homing of these cells from the bone marrow to the thymus as well as in the maturation of precursors to CD4+CD8+ thymocytes. 3) A positive correlation was observed between the expression of Ly-6 antigens on several clones of a polyoma virus transformed BALB/c 3T3 cell and the tumorigenicity of these clones. Moreover, tumors that appear following a relatively short latency period tend to express more Ly-6 than tumors appearing after a prolonged latency. These results raise the possibility that an in vivo encounter between an Ly-6 expressing tumor cell and an Ly-6 counter-receptor may confer upon the Ly-6 high expressor the high malignancy phenotype.